GEN-1

点击蓝字 关注我们 妇科癌症涵盖卵巢癌、子宫内膜癌、宫颈癌以及外阴与阴道恶性肿瘤，是全球范围内重要的公共卫生挑战。本文重点梳理Nabil Ismaili在《Biomedicines》期刊发表的一篇综述，介绍2025年卵巢癌研究方面的最新进展，以期为同行提供参考。 2025年卵巢癌研究交付了妇科肿瘤学年度最具范式转变意义的进展：突破免疫疗法壁垒，并且新机制药物不断取得突破。 铂耐药复发性卵巢癌的里程碑 在ESMO 2025全体会议上报告的ENGOT-ov65/KEYNOTE-B96试验具有里程碑意义[1]。这项全球性、双盲、III期试验评估了帕博利珠单抗联合每周紫杉醇（研究者酌情可选加贝伐珠单抗）对比安慰剂联合每周紫杉醇（±贝伐珠单抗）在既往接受过1-2线治疗、铂耐药复发性卵巢癌患者中的疗效。双重主要终点是PD-L1 CPS≥1患者（约占643例ITT人群的75%）的无进展生存（PFS）和总生存（OS）。在第二次预设的中期分析（数据截止日期：2025年3月5日；中位随访26.6个月），该试验达到了两个终点。在PD-L1 CPS≥1人群中，帕博利珠单抗显著改善了PFS（中位8.3 vs. 7.2个月；HR=0.72；p=0.0014），并且显著改善了OS（中位18.2 vs. 14.0个月；HR=0.76；p=0.0053），这是卵巢癌中首个基于免疫检查点抑制剂方案产生统计学显著性的OS改善。生存获益同样可在ITT人群中观察到（中位OS 17.7 vs. 14个月；HR=0.81；p=0.0114）。安全性特征与各药物已知特征一致。该试验确立了帕博利珠单抗+每周紫杉醇作为铂耐药复发性卵巢癌的新治疗标准。 新治疗机制的药物展现强大活性 发表在《柳叶刀》上的ROSELLA/ENGOT-ov68试验采用一种新的生物学策略。这项III期试验比较了白蛋白结合型紫杉醇联合relacorilant（一种选择性糖皮质激素受体调节剂）与单用白蛋白结合型紫杉醇在铂耐药复发性卵巢癌患者中的疗效[2]。该联合方案显著改善了主要终点BICR评估的PFS（中位5.7 vs. 3.8个月；HR=0.70；p<0.0001），并在中期分析中显示出显著的OS获益（中位15.97 vs. 11.5个月；HR=0.69；p=0.012）[3]。这验证了糖皮质激素受体调节是克服化疗耐药的可行治疗策略。 抗体偶联药物（ADC）继续显示出非凡前景。II期REJOICE-Ovarian01试验评估了raludotatug deruxtecan（一种靶向钙粘蛋白-6的ADC）在铂耐药复发性卵巢癌患者中的疗效。2025 ESMO报告的剂量优化部分的初步分析显示，在107例重度经治患者（中位既往4线治疗）中，确认的客观缓解率（ORR）为50.5%，完全缓解率为7.5%，中位PFS为7.8个月。值得注意的是，在不同水平的CDH6表达中均观察到活性，表明CDH6是卵巢癌中极具前景的靶点。该药物用于进一步研发的剂量为5.6 mg/kg[4]。 一些早期试验也报告了其他新药。INCB123667（一种选择性CDK2抑制剂）的I期研究在晚期铂耐药和难治性卵巢癌患者中显示出初步疗效信号和可控的安全性特征，突显CDK2可能是克服耐药的另一个潜在靶点[5]。此外，Lee等人报告了一项帕博利珠单抗和乐伐替尼在复发性透明细胞卵巢癌中的II期试验结果，在这种以预后差和对化疗耐药而闻名的组织学亚型中，该方案的治疗活性值得进一步研究[6]。 完善一线和维持治疗 针对高风险III/IV期上皮性卵巢癌的III期ICON8B试验的长期随访提供了关于化疗强度的重要数据[7]。中位随访72个月，与标准三周一次紫杉醇/卡铂/贝伐珠单抗相比，剂量密集的每周紫杉醇联合三周一次卡铂/贝伐珠单抗显著改善了OS（中位OS 49.8 vs. 39.6个月；HR=0.79；p=0.01）。这强化了剂量密集型化疗在含贝伐珠单抗方案中对于特定高风险患者的作用。 在维持治疗方面，FIRST/ENGOT-OV44试验评估了dostarlimab（抗PD-1）联合尼拉帕利（PARP抑制剂）作为晚期卵巢癌的一线维持治疗方案[8]。根据ASCO 2025报告，该试验显示，与尼拉帕利单药相比，联合治疗显著改善了PFS，尤其是在同源重组缺陷（HRD）阳性肿瘤中，表明在前期维持治疗中，免疫疗法与PARP抑制剂联合具有协同效应。 FZOCUS-1试验研究了氟唑帕利联合或不联合阿帕替尼（一种VEGFR2抑制剂）作为一线维持治疗。发表在《临床肿瘤学杂志》上的研究显示，与安慰剂组相比，氟唑帕利联合阿帕替尼显著延长了PFS，提供了一种新的维持治疗策略。这种方案在那些因BRCA基因状态或既往使用过贝伐珠单抗而可能限制PARP抑制剂使用的患者群体中，尤其具有意义[9]。 关于创新的给药方法，OVATION-2试验提供了腹腔内IMNN-001（一种TLR8激动剂）联合新辅助化疗的更新生存分析，结果显示出激活晚期卵巢癌局部免疫微环境可产生良好效果。更新分析显示，IMNN-001联合新辅助化疗的中位PFS为14.9个月，而新辅助化疗单药为11.9个月；中位OS分别为46.0个月和33.0个月[10]。 综上，ENGOT-ov65/KEYNOTE-B96显示免疫疗法在铂耐药患者中产生明确的生存获益，可以说是2025年妇科肿瘤学最具范式转变意义的发现，因为卵巢癌被认为是“免疫学冷肿瘤”，多项免疫检查点抑制剂单药或联合化疗的试验均告失败。ROSELLA试验验证了一个全新的靶点——糖皮质激素受体。Raludotatug deruxtecan的显著活性表明CDH6是一个极具前景的ADC靶点。ICON8B的长期OS获益强化了剂量密集型化疗在靶向治疗时代仍然具有重要意义，特别是对于高风险患者。FIRST试验关于dostarlimab-尼拉帕利维持治疗的阳性结果创造了一种新的、可能具有协同作用的前线治疗选择，尤其是在HRD阳性疾病中。在透明细胞癌中探索帕博利珠单抗-乐伐替尼等组合，有助于解决这种疾病未满足的临床需求。 参考文献 （上下滑动可查看） 1. Colombo, N. et al. Pembrolizumab vs placebo plus weekly paclitaxel ± bevacizumab in platinum-resistant recurrent ovarian cancer: Results from the randomized double-blind phase III ENGOT-ov65/KEYNOTE-B96 study. Ann. Oncol. 2025, 36, LBA3. 2. Olawaiye, A. et al. ROSELLA: A Phase 3 Study of Relacorilant in Combination with Nab-Paclitaxel versus Nab-Paclitaxel Monotherapy in Patients with Platinum-Resistant Ovarian Cancer. J. Clin. Oncol. 2025, 43, LBA5507.  3. Olawaiye, A.B. et al. Relacorilant and nab-paclitaxel in patients with platinum-resistant ovarian cancer (ROSELLA): An open-label, randomised, controlled, phase 3 trial. Lancet 2025, 405, 2205–2216.  4. Ray-Coquard, I.L. et al. LBA42 Raludotatug Deruxtecan (R-DXd) in Patients with Platinum-Resistant Ovarian Cancer: Primary Analysis of the Phase II Dose-Optimization Part of REJOICE-Ovarian01. Ann. Oncol. 2025, 36, S1585–S1586. 5. Damian, S. et al. Safety and Preliminary Efficacy from a Phase 1 Study of INCB123667, a Selective CDK2 Inhibitor, in Patients with Advanced Platinum-Resistant and Refractory Ovarian Cancer. J. Clin. Oncol. 2025, 43, 5514.  6. Lee, E.K. et al. A Phase II Trial of Pembrolizumab and Lenvatinib in Recurrent or Persistent Clear Cell Ovarian Carcinoma. J. Clin. Oncol. 2025, 43, 5515.  7. Clamp, A. et al. ICON8B: GCIG Phase III Randomised Trial Comparing First-Line Weekly Dose-Dense Chemotherapy + Bevacizumab to Three-Weekly Chemotherapy + Bevacizumab in High-Risk Stage III–IV Epithelial Ovarian Cancer: Final Overall Survival Analysis. Ann. Oncol. 2025, 36, 1064O.  8. Hardy-Bessard, A.-C. et al. FIRST/ENGOT-OV44: A Phase 3 Clinical Trial of Dostarlimab and Niraparib in First-Line Advanced Ovarian Cancer. J. Clin. Oncol. 2025, 43, LBA5506.  9. Wu, L. et al. Fuzuloparib with or without apatinib as maintenance therapy in newly diagnosed, advanced ovarian cancer (FZOCUS-1): A multicenter, randomized, double-blind, placebo-controlled phase 3 trial. CA Cancer J. Clin. 2026, 76, e70042.  10. Thaker, P.H. et al. A Phase I/II Study of the Safety and Efficacy of Intraperitoneal IMNN-001 in Combination with Neoadjuvant Chemotherapy of Paclitaxel and Carboplatin in Patients Newly Diagnosed with Advanced Epithelial Ovarian Cancer: Updated Survival Analysis from OVATION-2 Trial. J. Clin. Oncol. 2025, 43, 5516. （来源：《肿瘤瞭望》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

Enrollment in the Pivotal Phase 3 OVATION 3 Study Advances Company Toward Future BLA Filing New Data from MRD Study Reinforces IMNN-001's Promise as a Potential Breakthrough Immunotherapy LAWRENCEVILLE, N.J. , Dec. 29, 2025 (GLOBE NEWSWIRE) -- IMUNON , Inc. (Nasdaq: IMNN) Dear Valued Shareholders, 2025, A Year of Momentum: Advancing Toward a Potential Breakthrough in Ovarian Cancer Treatment As we close out 2025, I am excited to reflect on a year marked by significant clinical progress, robust data validation, and strategic execution that has significantly strengthened IMUNON's position. Our focus on harnessing the power to activate the body's immune system against cancer has yielded compelling results, bringing us closer to delivering innovative therapies that could transform patient outcomes and create substantial value for you, our shareholders. Very importantly, we believe that we are well positioned for an equally successful 2026. One Step Closer to BLA Filing: Strong Progress in the Phase 3 OVATION 3 Study This year, we initiated and advanced our pivotal Phase 3 OVATION 3 Study evaluating IMNN-001 in combination with standard-of-care neoadjuvant and adjuvant chemotherapy for women with newly diagnosed advanced ovarian cancer. Enrollment continues to generate strong interest, underscoring the enthusiasm from investigators and the medical community for this potential sea change in the standard of care for this underserved population. This momentum is another metric illustrating the meaningful clinical outcomes observed in our Phase 2 OVATION 2 Study, where IMNN-001 demonstrated a 13-month extension in median overall survival ( OS) in the intent-to-treat population (hazard ratio of 0.70). In patients receiving PARP inhibitors as maintenance therapy, the median OS in the IMNN-001 arm has not yet been reached, with all patients having surpassed 31 months of follow-up and numerous patients progressing beyond five years (vs. 37 months in the control arm; hazard ratio of 0.42). These results, presented at ASCO and published in Gynecologic Oncology, continue to highlight IMNN-001's potential to redefine frontline treatment, where no meaningful advances have occurred in over 30 years. Renewing the Promise of Immunotherapy: New Insights from the Ongoing MRD Study Building on this foundation, new data from our ongoing minimal residual disease (MRD) study—conducted in partnership with Break Through Cancer—further renew the promise of a novel immunotherapy for frontline ovarian cancer. Translational data demonstrate IMNN-001's broad impact on the tumor microenvironment, with definitive evidence that treatment leads to IL-12 production by macrophages in tumor tissue, boosting T cell cytotoxic functions. Specifically: Macrophage activation: IMNN-001 induces robust expression of IL12A and IL12B in macrophages of peritoneal fluid and tumor tissue, stimulating a cascade of anti-tumor cytokines, including interferon-gamma, and resulting in potent macrophage and T cell activation. Tumor microenvironment remodeling: The tumor immune microenvironment becomes more inflamed following exposure to IMNN-001, effectively turning "cold" tumors "hot" by activating both innate and adaptive immune systems. Preliminary clinical readouts from the MRD study are equally encouraging, showing a lower MRD positivity rate, a lower percentage of tumor-containing biopsies in MRD-positive patients, higher complete response scores (CRS) at cytoreduction, and a higher probability of progression-free survival (PFS) with IMNN-001 compared to the control arm. The positive tolerability profile of IMNN-001 continues, including in combination with standard-of-care chemotherapy plus bevacizumab and also in the maintenance setting, with no cytokine release syndrome, systemic toxicities, or serious immune-related adverse events observed. The consistency of evidence across our trials—OVATION 1, OVATION 2, MRD and now OVATION 3 —with IMNN-001's favorable benefit/risk profile, gives us strong hope for a potential breakthrough in treating newly diagnosed ovarian cancer, a disease affecting 20,000 women annually in the U.S. and 300,000 worldwide, with high recurrence and low five-year survival rates. TheraPlas Platform: Expanding Horizons Beyond Ovarian Cancer Our TheraPlas platform, which enables localized, durable expression of interleukin-12 (IL-12) and other therapeutic payloads, continues to validate its potential. By targeting the tumor site directly, our unique approach avoids the toxicities of systemic immunotherapies while remodeling the microenvironment to generate anti-tumor responses. We have an extensive set of completed animal experiments with IMNN-001 in additional tumor types and TheraPlas for other DNA plasmid delivered payloads, which could unlock growth opportunities through partnerships, including potential licensing in Asia-Pacific regions. Financial Discipline and Outstanding Execution Throughout 2025, we maintained financial discipline, conserving cash while securing resources to support our pivotal trial. Our cGMP-compliant manufacturing has reduced costs significantly, which may position us for high gross margins upon potential FDA approval. The resiliency in our share price, even amidst what we believe to be extreme short positions, and interest from institutional investors reflect growing confidence in our science and strategy. We remain committed to strategic funding of the OVATION 3 trial, estimated at $30 million for the HRD+ subgroup focus, with options for expansion. Looking Ahead: A Pivotal 2026 and Beyond As we enter 2026, IMUNON is poised for key milestones, including continued enrollment in OVATION 3 with interim analyses potentially enabling early stopping and BLA filing in the HRD+ population. We anticipate additional data presentations at major conferences, further translational insights from OVATION 2 tumor samples, and progress on business development initiatives. With Fast Track and Orphan Drug designations in place, we are dedicated to bringing IMNN-001 to patients in need while driving sustainable shareholder value. On behalf of the IMUNON team, thank you for your unwavering support. Together, we are on the cusp of redefining cancer care. Sincerely, Stacy R. Lindborg , Ph.D.President and Chief Executive Officer IMUNON, Inc. Forward-Looking Statements IMUNON wishes to inform readers that forward-looking statements in this letter are made pursuant to the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical fact, including, but not limited to, statements regarding the timing and enrollment of the Company’s clinical trials, the potential of any therapies developed by the Company to fulfill unmet medical needs, the market potential for the Company’s products, if approved, the potential efficacy and safety profile of our product candidates, and the Company’s plans and expectations with respect to its development programs more generally, are forward-looking statements. We generally identify forward-looking statements by using words such as “may,” “will,” “expect,” “plan,” “anticipate,” “estimate,” “intend” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances). Readers are cautioned that such forward-looking statements involve risks and uncertainties including, without limitation, uncertainties relating to unforeseen changes in the course of research and development activities and in clinical trials, including the fact that interim results are not necessarily indicative of final results; the uncertainties of and difficulties in analyzing interim clinical data; the significant expense, time and risk of failure in conducting clinical trials; the need for IMUNON to evaluate its future development plans; possible actions by customers, suppliers, competitors or regulatory authorities; and other risks detailed from time to time in IMUNON’s filings with the Securities and Exchange Commission. IMUNON assumes no obligation, except to the extent required by law, to update or supplement forward-looking statements that become untrue because of subsequent events, new information or otherwise. Contacts: Source: Imunon, Inc.